Purpose. This limited competition FOA is to continue the Long Life
Family Study (LLFS). The LLFS was designed to determine the degree and
patterns of familial transmission and aggregation of exceptional longevity and
healthy survival to advanced age as characterized by a variety of phenotypic
measures, with a further goal of also understanding potential genetic factors
that contribute to exceptional survival. Five awards,
to four study centers and one data management and coordinating center, were
made in response to RFA-AG-03-004.

Mechanism of Support. This FOA
will utilize the National Institutes of Health (NIH) cooperative agreement
(U01) grant mechanism.

Funds Available and Anticipated Number
of Awards.The NIA intends to commit $8.4
million total costs beginning in FY2010, and out year total costs up to $6.0
million in FY2011 and out year total costs up to $5.2 million in FY2012 to fund
up to five awards.

Budget and Project Period. Thetotal project
period for an application submitted in response to this funding opportunity may
not exceed three years. For the Data Management and Coordinating Center, direct costs are limited to $5.2M in FY2010, $2.7M in FY2011 and $1.7M in FY2012. For
the Study Centers, direct costs may not exceed $503,000 in FY2010, $530,000 in
FY2011, and $543,000 in FY2012.

Eligible
Institutions/Organizations.The only
eligible organizations are the current recipients of the LLFS Awards
funded through RFA-AG-03-004.

Eligible Project
Directors/Principal Investigators (PDs/PIs). Individuals with the
skills, knowledge, and resources necessary to carry out the proposed research are invited to work with their
institution/organization to develop an application for support.
Individuals from underrepresented racial and ethnic groups as well as
individuals with disabilities are always encouraged to apply for NIH
support.

Number of PDs/PIs. More than
one PD/PI (i.e., multiple PDs/PIs), may be designated on the application.

Number
of Applications.Each of the five current
LLFS awardees may submit one application.

Resubmissions.Resubmission applications are not
permitted in response to this FOA

Renewals.Renewal applications are permitted in
response to this FOA

Special Date(s). This FOA uses
non-standard due dates. See Receipt, Review and Anticipated Start Dates

A primary public health objective of aging research is to
identify ways to help people be as healthy as possible, as long as
possible. Research provides evidence that individuals who live to
extremely old ages tend to have maintained good health throughout most of their
lives, suggesting that exceptionally long life is associated with protective
factors that confer an exceptionally long “health span”.
Familial factors appear to contribute to exceptional longevity, as illustrated
by the fact that siblings of exceptionally long-lived people have a higher
probability of surviving to extremely old age than the average population, and
that this probability is especially high if the siblings come from families
with many exceptionally long-lived members. There is also evidence of a genetic
basis for at least some of the familial clustering of exceptional longevity
from association studies and genome-wide analysis.

Recognizing
the potential of a study of multiple generations in families with exceptionally
long-lived individuals to identify factors that contribute to unusually long
and healthy life, the NIA issued the Request for Applications
(RFA) AG-03-004, “The National Institute on Aging Multicenter Study
on Exceptional Survival in Families” (http://grants.nih.gov/grants/guide/rfa-files/RFA-AG-03-004.html) in 2003. The purpose of this FOA was to determine the degree and
patterns of familial transmission and aggregation of exceptional longevity and
healthy survival to advanced age as characterized by a variety of phenotypic
measures, with a further goal of also understanding potential genetic factors
that contribute to exceptional survival. Five awards, to four study centers
and one data management and coordinating center (DMCC), were made in response
to this FOA.

The
currently funded investigators have successfully developed and implemented the
LLFS study protocols during the first five years and they possess the necessary
infrastructure, organization, and leadership to successfully pursue the goals
of the next phase. They have (1) developed a comprehensive protocol to
pursue the characterization of exceptional survival in families, (2) recruited
and collected comprehensive phenotypic data and blood for genetic analysis from
long-lived families, (3) initiated the analysis of phenotypic data, and (4)
developed plans for the genetic analysis, making them uniquely qualified to
carry out the next phase of the study.

The first
phase of the LLFS focused on the development of a comprehensive protocol
covering the domains of health, function, lifestyle, and socioeconomic status,
large-scale recruitment of families with high proportions of long-lived
members, collection of phenotypic data and biospecimens, and a limited number
of biochemical analyses of specimens. Genetic analyses were not part of the
first phase of the study, but blood/DNA is being collected from all study
participants in anticipation of this analysis in the next phase of the study.

The goals of
the second phase of LLFS are to conduct additional biochemical analysis of
specimens, genotyping, telephone follow-up of participants’ status, and
analyze relationships of genetic factors to phenotypes relating to exceptional
survival. Applicants should provide a detailed proposal
for the second phase of LLFS that addresses the following objectives:

Phenotypic
characterization of participant families through biochemical analysis of
additional blood assays and biomarkers for healthy aging on stored samples
collected in the first phase of LLFS. Analysis plans for assessing the
heritability of the phenotypes measured in the selected assays should be
described.

Genetic analysis of DNA samples collected from participant
families in the first phase of LLFS. Plans should include the proposed
genotyping methodology.

A detailed plan for how the phenotypic data
collected in LLFS will be analyzed along with the genotypic data generated in
the second phase of LLFS to understand potential genetic influences on healthy
aging and longevity traits. Analysis plans should include
strategies for potential common variants (e.g., genome wide association scan),
and for potential multiple rare variants that may be found only in certain
families (e.g., genome wide linkage scan). Strategies to identify and
localize associated rare variants for healthy aging and longevity by
resequencing candidate genes in study participants should also be described.

A description of what new information will be
collected from study participants in the second phase of LLFS and how it will
strengthen the analyses genotype-phenotype relationships and potential
gene-environment interactions that affect healthy aging and longevity.

Plans for long-term storage of biospecimens
and archiving and sharing data.

Each
re-competing U01 is expected to provide a multidisciplinary structure and study
plan that will accommodate genetic analysis and assays of collected blood,
telephone follow-up of participants’ status. Applicants should describe
the resources, staffing, and time interval needed to accomplish each objective.
NIA decisions on funding will be made on the basis of scientific merit and
availability of funds. A project period of up to three years may be proposed.

This funding
opportunity will use the NIH cooperative agreement award (U01) mechanism.
The Project Director/Principal Investigator (PD/PI) will be solely responsible
for planning, directing, and executing the proposed project.

This funding opportunity
will use a cooperative agreement award mechanism. In
the cooperative agreement mechanism, the Project Director/Principal
Investigator (PD/PI) retains the primary responsibility and dominant role for
planning, directing, and executing the proposed project, with NIH staff being
substantially involved as a partner with the Principal Investigator, as
described under the Section VI. 2. Administrative
Requirements,
"Cooperative Agreement Terms and Conditions of Award".

The
NIA expects to invite renewal applications for this program at the end of this
funding period.

2. Funds Available

The NIA intends to commit $8.4 million total
costs beginning in FY2010, and out year total costs of up to $6.0 million in
FY2011 and out year total costs of up to $5.2 million in FY2012. The
NIA intends to fund up to five awards in response to
this FOA and the total project period for an application submitted in
response to this funding opportunity may not exceed three years.

For
the Data Management and Coordinating Center, direct costs are limited to $5.2M
in FY2010, $2.7M in FY2011 and $1.7M in FY2012. For the Study Centers, direct
costs may be up to but not exceed $503,000 in FY2010, $530,000 in FY2011, and
$543,000 in FY2012.

Future
year amounts, beyond FY2010, will depend on annual appropriations.

Because the nature
and scope of the proposed research will vary from application to application,
it is anticipated that the size and duration of each award will also vary.
Although the financial plans of the IC(s) provide support for this program, awards
pursuant to this funding opportunity are contingent upon the availability of
funds and the receipt of a sufficient number of meritorious applications.

Facilities and
administrative costs requested by consortium participants are not included in
the direct cost limitation, see NOT-OD-05-004.

Any
individualwith the skills, knowledge, and resources necessary to
carry out the proposed research as the PD/PI is invited to work with his/her
institution to develop an application for support. Individuals from
underrepresented racial and ethnic groups as well as individuals with
disabilities are always encouraged to apply for NIH support.

Applications must be
prepared using the most current PHS 398 research grant application instructions
and forms. Applications must have a D&B Data Universal Numbering System
(DUNS) number as the universal identifier when applying for Federal grants or
cooperative agreements. The D&B number can be obtained by calling (866)
705-5711 or through the web site at http://www.dnb.com/us/. The D&B number should
be entered on line 11 of the face page of the PHS 398 form.

The title and
number of this funding opportunity must be typed in item (box) 2 only of the
face page of the application form and the YES box must be checked.

Every effort should be made to comply with the
format specifications, which are based upon a standard U.S. paper size of 8.5” x 11” within each PDF.

Funds for up to 8% Facilities and Administrative
(F&A) costs (excluding equipment) may be requested. SeeNOT-OD-01-028, March 29,
2001.

Organizations must comply with Federal/NIH
policies on human subjects, animals, and biohazards.

Organizations must comply with Federal/NIH
biosafety and biosecurity regulations. See Section VI.2., “Administrative
and National Policy Requirements”

Proposed research should provide special
opportunities for furthering research programs through the use of unusual
talent, resources, populations, or environmental conditions in other countries
that are not readily available in the United States or that augment existing U.S. resources.

3.
Submission Dates and Times

Applications must be
received on or before the receipt date described below (Section IV.3.A). Submission times N/A.

Applications must be
prepared using the forms found in the PHS 398 instructions for preparing a
research grant application. Submit a signed, typewritten original of the
application, including the checklist, and three signed photocopies in one
package to:

Applications must be received on or before the
application receipt date) described above (Section IV.3.A.). If an application is
received after that date, the application may be delayed in the review process
or not reviewed. Upon receipt, applications will be evaluated for
completeness by the CSR and for responsiveness by the reviewing Institute
Incomplete and/or non-responsive applications will not be reviewed.

The NIH will not
accept any application in response to this funding opportunity that is
essentially the same as one currently pending initial review, unless the
applicant withdraws the pending application. However, when a previously
unfunded application, originally submitted as an investigator-initiated
application, is to be submitted in response to a funding opportunity, it is to
be prepared as a NEW application. That is, the application for the funding
opportunity must not include an Introduction describing the changes and
improvements made, and the text must not be marked to indicate the changes from
the previous unfunded version of the application.

All NIH awards are
subject to the terms and conditions, cost principles, and other considerations
described in the NIH Grants Policy Statement. The Grants Policy Statement can
be found at NIH Grants Policy
Statement.

Pre-award costs
are allowable. A grantee may, at its own risk and without NIH prior approval,
incur obligations and expenditures to cover costs up to 90 days before the
beginning date of the initial budget period of a new or renewal award if such
costs: 1) are necessary to conduct the project, and 2) would be allowable under
the grant, if awarded, without NIH prior approval. If specific expenditures
would otherwise require prior approval, the grantee must obtain NIH approval
before incurring the cost. NIH prior approval is required for any costs to be
incurred more than 90 days before the beginning date of the initial budget
period of a new or renewal award.

The incurrence
of pre-award costs in anticipation of a competing or non-competing award
imposes no obligation on NIH either to make the award or to increase the amount
of the approved budget if an award is made for less than the amount anticipated
and is inadequate to cover the pre-award costs incurred. NIH expects the
grantee to be fully aware that pre-award costs result in borrowing against
future support and that such borrowing must not impair the grantee's ability to
accomplish the project objectives in the approved time frame or in any way
adversely affect the conduct of the project (see NIH Grants Policy Statement http://grants.nih.gov/archive/grants/policy/nihgps_2003/index.htm.)

6. Other Submission Requirements

Awardees
must agree to the “Cooperative Agreement Terms and Conditions of
Award” in Section VI.2.A “Award Administration Information.

Do not use
the Appendix to circumvent the page limitations of the Research Plan component.
An application that does not observe the required page limitations may be
delayed in the review process.

Resource Sharing
Plan(s)

NIH considers the sharing of unique research
resources developed through NIH-sponsored research an important means to
enhance the value of, and advance research. When resources have been developed
with NIH funds and the associated research findings published or provided to
NIH, it is important that they be made readily available for research purposes
to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing,
this must be explained in Resource Sharing section of the application. See http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm.

(b) Sharing Model Organisms:
Regardless of the amount requested, all applications where the development of
model organisms is anticipated are expectedto include a
description of a specific plan for sharing and distributing unique model
organisms and related resources, or state appropriate reasons why such sharing
is restricted or not possible. See Sharing Model Organisms Policy, and NIH Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless
of the amount requested, applicants seeking funding for a genome-wide
association study are expected to provide a plan for submission of GWAS data to the NIH-designatedGWAS data repository, or provide an appropriate
explanation why submission to the repository is not possible. A
genome-wide association study is defined as any study of genetic variation
across the entire genome that is designed to identify genetic associations with
observable traits (such as blood pressure or weight) or the presence or absence
of a disease or condition. For further information see Policy for Sharing
of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies, NIH Guide
NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.

Section
V. Application Review Information

1. Criteria

Only the review
criteria described below will be considered in the review process.

2. Review and Selection Process

Applications
that are complete and responsive to the FOA will be evaluated for scientific and
technical merit by an appropriate peer review group convened by NIA and in accordance with NIH peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria
stated below.

As part of the scientific peer
review, all applications will:

Undergo
a selection process in which only those applications deemed to have the
highest scientific and technical merit, generally the top half of
applications under review, will be discussed and assigned an
impact/priority score.

Receive
a written critique.

Receive
a second level of review by the National Advisory Council on Aging

The
following will be considered in making funding decisions:

Scientific
and technical merit of the proposed project as determined by peer review

Availability
of funds

Relevance of the
proposed project to program priorities

The mission of the NIH is to support science
in pursuit of knowledge about the biology and behavior of living systems and to
apply that knowledge to extend healthy life and reduce the burdens of illness
and disability. As part of this mission, applications submitted to the
NIH for grants or cooperative agreements to support biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Overall
Impact. Reviewers will provide an overall
impact/priority score to reflect their assessment of the likelihood for the
project to exert a sustained, powerful influence on the research field(s)
involved, in consideration of the following five core review criteria, and
additional review criteria (as applicable for the project proposed).

Core Review
Criteria. Reviewers will consider each of the five
review criteria below in the determination of scientific and technical merit,
and give a separate score for each. An application does not need to be
strong in all categories to be judged likely to have major scientific
impact. For example, a project that by its nature is not innovative may
be essential to advance a field.

Significance. Does the project address an important problem or a critical
barrier to progress in the field? If the aims of the project are
achieved, how will scientific knowledge, technical capability, and/or clinical
practice be improved? How will successful completion of the aims change
the concepts, methods, technologies, treatments, services, or preventative
interventions that drive this field?

Investigator(s). Are the PD/PIs, collaborators, and other researchers well suited
to the project? If Early Stage Investigators or New Investigators, do
they have appropriate experience and training? If established, have they
demonstrated an ongoing record of accomplishments that have advanced their
field(s)? If the project is collaborative or multi-PD/PI, do the
investigators have complementary and integrated expertise; are their leadership
approach, governance and organizational structure appropriate for the project?

Innovation. Does the application challenge and seek
to shift current research or clinical practice paradigms by utilizing novel
theoretical concepts, approaches or methodologies, instrumentation, or
interventions? Are the concepts, approaches or methodologies,
instrumentation, or interventions novel to one field of research or novel in a
broad sense? Is a refinement, improvement, or new application of
theoretical concepts, approaches or methodologies, instrumentation, or
interventions proposed?

Approach. Are the overall strategy, methodology, and analyses well-reasoned
and appropriate to accomplish the specific aims of the project? Are
potential problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development,
will the strategy establish feasibility and will particularly risky aspects be
managed?
If the project involves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?

Environment. Will
the scientific environment in which the work will be done contribute to the
probability of success? Are the institutional support, equipment and
other physical resources available to the investigators adequate for the
project proposed? Will the project benefit from unique features of the
scientific environment, subject populations, or collaborative
arrangements?

Additional
Review Criteria. As applicable for the project proposed,
reviewers will consider the following additional items in the
determination of scientific and technical merit, but will not give separate
scores for these items.

Protections
for Human Subjects. For research that
involves human subjects but does not involve one of the six categories of
research that are exempt under 45 CFR Part 46, the committee will evaluate the
justification for involvement of human subjects and the proposed protections
from research risk relating to their participation according to the following
five review criteria: 1) risk to subjects, 2) adequacy of protection against
risks, 3) potential benefits to the subjects and others, 4) importance of the
knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research
that involves human subjects and meets the criteria for one or more of
the six categories of research that are exempt under 45 CFR Part 46, the
committee will evaluate: 1) the justification for the exemption, 2) human
subjects involvement and characteristics, and 3) sources of materials.

Inclusion
of Women, Minorities, and Children. When
the proposed project involves clinical research, the committee will evaluate
the proposed plans for inclusion of minorities and members of both genders, as
well as the inclusion of children.

Vertebrate
Animals. The committee will evaluate the
involvement of live vertebrate animals as part of the scientific assessment
according to the following five points: 1) proposed use of the animals, and
species, strains, ages, sex, and numbers to be used; 2) justifications for the
use of animals and for the appropriateness of the species and numbers proposed;
3) adequacy of veterinary care; 4) procedures for limiting discomfort,
distress, pain and injury to that which is unavoidable in the conduct of
scientifically sound research including the use of analgesic, anesthetic, and
tranquilizing drugs and/or comfortable restraining devices; and 5) methods of
euthanasia and reason for selection if not consistent with the AVMA Guidelines
on Euthanasia.

Renewal
Applications. When reviewing a Renewal application
(formerly called a competing continuation application), the committee will
consider the progress made in the last funding period.

Biohazards. Reviewers will assess whether materials or procedures proposed are
potentially hazardous to research personnel and/or the environment, and if
needed, determine whether adequate protection is proposed.

Additional
Review Considerations. As applicable for the project proposed,
reviewers will address each of the following items, but will not give scores
for these items and should not consider them in providing an overall
impact/priority score.

Budget
and Period Support. Reviewers will
consider whether the budget and the requested period of support are fully
justified and reasonable in relation to the proposed research.

Select
Agent Research. Reviewers will assess the information
provided in this section of the application, including 1) the Select Agent(s)
to be used in the proposed research, 2) the registration status of all entities
where Select Agent(s) will be used, 3) the procedures that will be used to
monitor possession use and transfer of Select Agent(s), and 4) plans for
appropriate biosafety, biocontainment, and security of the Select Agent(s).

Applications
from Foreign Organizations.
Reviewers will assess whether the project presents special opportunities for
furthering research programs through the use of unusual talent, resources,
populations, or environmental conditions that exist in other countries and
either are not readily available in the United States or augment existing U.S. resources.

A
formal notification in the form of a Notice of Award (NoA) will be
provided to the applicant organization. The NoA signed by the grants management
officer is the authorizing document. Once all administrative and programmatic
issues have been resolved, the NoA will be generated via email notification
from the awarding component to the grantee business official (designated in
item 12 on the Application Face Page). If a grantee is not email enabled, a
hard copy of the NoA will be mailed to the business official.

Selection of an application for award is not an
authorization to begin performance. Any costs incurred before receipt of the
NoA are at the recipient's risk. These costs may be reimbursed only to the
extent considered allowable pre-award costs. See Also Section
IV.5. Funding Restrictions.

The
following Terms and Conditions will be incorporated into the award statement
and will be provided to the Principal Investigator as well as to the
appropriate institutional official, at the time of award.

2.A. Cooperative Agreement Terms and Conditions of
Award

The following special
terms of award are in addition to, and not in lieu of, otherwise applicable OMB
administrative guidelines, HHS grant administration regulations at 45 CFR Parts
74 and 92 (Part 92 is applicable when State and local Governments are eligible
to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and
funding instrument used for this program will be the cooperative agreement an
"assistance" mechanism (rather than an "acquisition"
mechanism), in which substantial NIH programmatic involvement with the awardees
is anticipated during the performance of the activities. Under the cooperative
agreement, the NIH purpose is to support and stimulate the recipients'
activities by involvement in and otherwise working jointly with the award
recipients in a partnership role; it is not to assume direction, prime
responsibility, or a dominant role in the activities. Consistent with this
concept, the dominant role and prime responsibility resides with the awardees
for the project as a whole, although specific tasks and activities may be
shared among the awardees and the NIH as defined below.

2.
A.1. Principal Investigator Rights and Responsibilities

The Principal
Investigator will have the primary responsibility for defining objectives and approaches; participant follow-up, quality control, data
analyses and interpretation, and for preparation of publications for their
projects. PIs at the Study Centers shall retain custody of, and primary rights
to, the site-specific data developed under their award, subject to Government
rights of access, consistent with current HHS, PHS, and NIH policies. In
addition, awardees will engage in collaborative activities through
participation in Steering Committee meetings and potential conference calls in
the development and implementation of common measures across Study Centers. The
Steering Committee will define the rules regarding access to, and publication
of, findings from analyses of common data.

The Study
Centers will work collaboratively to perform analyses for the LLFS Study as
approved by the Steering Committee. Study Center PIs will be expected to
maintain close communications with the NIA Project Scientist and the Data
Management and Coordinating Center (DMCC).

The DMCC
will be involved in collaborations with the NIA and the LLFS Study Centers. The DMCC is responsible for working cooperatively with Study Centers and sponsoring organizations in a multicenter study and in overseeing the
implementation of, and adherence to, a common protocol, as well as assuring
quality control of the data collected. In addition to organizing and attending
regular meetings, the DMCC will be expected to maintain close communications
with the NIA Project Scientist and the PIs of the LLFS Study Center.

Awardees
will retain custody of and have primary rights to the data and software
developed under these awards, subject to Government rights of access consistent
with current HHS, PHS, and NIH policies.

2.
A.2. NIH Responsibilities

An NIA Project
Scientist will have substantial programmatic involvement that is above and
beyond the normal stewardship role in awards, as described below.

The project scientist will participate in the
monitoring of issues relating to recruitment, data collection, quality control,
and analyses, and assist in the development and/or adjustment of study
protocols.

Additionally, an agency program official or IC program
director will be responsible for the normal scientific and programmatic
stewardship of the award and will be named in the award notice.

2.A.3.
Collaborative Responsibilities

A Steering Committee will serve as the main
decision-making body for the shared aspects of the study. The PIs of the Study
Centers, the PI of the DMCC, and the designated NIA Project Scientist will
comprise the voting members of the Steering Committee. Appropriate DMCC staff
should also attend the Steering Committee Meetings. The Steering Committee will
meet every three to six months, or as needed.

An Observational Study Monitoring Board (OSMB) will
periodically review the research progress and the safety of the study subjects
on a regular basis, and will resolve any serious conflicts over how the overall
study should proceed. The OSMB will be established by NIA staff and approved by
the Director, NIA, and will be comprised of experts in relevant clinical,
statistical, and bioethical fields. The Chairperson of the Steering Committee
and the NIA Project Scientist will participate as non-voting members of the
OSMB.

2.A.4. Dispute Resolution

Any disagreements that
may arise in scientific or programmatic matters (within the scope of the award)
between award recipients and the NIH may be brought to arbitration. A Dispute
Resolution Panel composed of three members will be convened. It will have three
members: a designee of the Steering Committee chosen without NIH staff voting,
one NIH designee, and a third designee with expertise in the relevant area who
is chosen by the other two; in the case of individual disagreement, the first
member may be chosen by the individual awardee. This special dispute resolution
procedure does not alter the awardee's right to appeal an adverse action that
is otherwise appealable in accordance with PHS regulations 42 CFR Part 50,
Subpart D and HHS regulations 45 CFR Part 16.

A
final progress report, invention statement, and Financial Status Report are
required when an award is relinquished when a recipient changes institutions or
when an award is terminated.

Section
VII. Agency Contacts

We
encourage your inquiries concerning this funding opportunity and welcome the
opportunity to answer questions from potential applicants. Inquiries may fall
into three areas: scientific/research, peer review, and financial or grants
management issues:

Human
Subjects Protection:Federal
regulations (45CFR46) require that applications and proposals involving human
subjects must be evaluated with reference to the risks to the subjects, the
adequacy of protection against these risks, the potential benefits of the
research to the subjects and others, and the importance of the knowledge gained
or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and
Safety Monitoring Plan:Data and safety
monitoring is required for all types of clinical trials, including physiologic
toxicity and dose-finding studies (phase I); efficacy studies (Phase II);
efficacy, effectiveness and comparative trials (Phase III). Monitoring should
be commensurate with risk. The establishment of data and safety monitoring
boards (DSMBs) is required for multi-site clinical trials involving
interventions that entail potential risks to the participants (NIH Policy for
Data and Safety Monitoring, NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:Investigators
submitting an NIH application seeking $500,000 or more in direct costs in any
single year are expected to include a plan for data sharing or state why this
is not possible (http://grants.nih.gov/grants/policy/data_sharing).

Investigators
should seek guidance from their institutions, on issues related to
institutional policies and local IRB rules, as well as local, State and Federal
laws and regulations, including the Privacy Rule. Reviewers will consider the
data sharing plan but will not factor the plan into the determination of the
scientific merit or the priority score.

Policy
for Genome-Wide Association Studies (GWAS):NIH is interested in advancing genome-wide association
studies (GWAS) to identify common genetic factors that influence health and
disease through a centralized GWAS data repository. For the purposes of this
policy, a genome-wide association study is defined as any study of genetic
variation across the entire human genome that is designed to identify genetic
associations with observable traits (such as blood pressure or weight), or the
presence or absence of a disease or condition. All applications, regardless of
the amount requested, proposing a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designated GWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. Data repository management (submission and access)
is governed by the Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies, NIH
Guide NOT-OD-07-088. For additional information,
see http://grants.nih.gov/grants/gwas/

Access
to Research Data through the Freedom of Information Act:The Office of
Management and Budget (OMB) Circular A-110 has been revised to provide access
to research data through the Freedom of Information Act (FOIA) under some
circumstances. Data that are (1) first produced in a project that is supported
in whole or in part with Federal funds and (2) cited publicly and officially by
a Federal agency in support of an action that has the force and effect of law
(i.e., a regulation) may be accessed through FOIA. It is important for
applicants to understand the basic scope of this amendment. NIH has provided
guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this
funding opportunity in a public archive, which can provide protections for the
data and manage the distribution for an indefinite period of time. If so, the
application should include a description of the archiving plan in the study
design and include information about this in the budget justification section
of the application. In addition, applicants should think about how to structure
informed consent statements and other human subjects procedures given the
potential for wider use of data collected under this award.

Sharing of Model
Organisms:NIH is committed to
support efforts that encourage sharing of important research resources including
the sharing of model organisms for biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of
grantees and contractors to elect and retain title to subject inventions
developed with Federal funding pursuant to the Bayh Dole Act (see the NIH Grants Policy Statement http://grants.nih.gov/archive/archive/grants/policy/nihgps_2003/index.htm). All investigators submitting an NIH application or
contract proposal, beginning with the October 1, 2004 receipt date, are
expected to include in the application/proposal a description of a specific
plan for sharing and distributing unique model organism research resources
generated using NIH funding or state why such sharing is restricted or not
possible. This will permit other researchers to benefit from the resources
developed with public funding. The inclusion of a model organism sharing plan
is not subject to a cost threshold in any year and is expected to be included
in all applications where the development of model organisms is anticipated.

Inclusion of Women
And Minorities in Clinical Research:It is the policy of the
NIH that women and members of minority groups and their sub-populations must be
included in all NIH-supported clinical research projects unless a clear and
compelling justification is provided indicating that inclusion is inappropriate
with respect to the health of the subjects or the purpose of the research. This
policy results from the NIH Revitalization Act of 1993 (Section 492B of Public
Law 103-43). All investigators proposing clinical research should read the
"NIH Guidelines for Inclusion of Women and Minorities as Subjects in
Clinical Research (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the
updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy
incorporates: the use of an NIH definition of clinical research; updated racial
and ethnic categories in compliance with the new OMB standards; clarification
of language governing NIH-defined Phase III clinical trials consistent with the
new PHS Form 398; and updated roles and responsibilities of NIH staff and the
extramural community. The policy continues to require for all NIH-defined Phase
III clinical trials that: a) all applications or proposals and/or protocols
must provide a description of plans to conduct analyses, as appropriate, to
address differences by sex/gender and/or racial/ethnic groups, including
subgroups if applicable; and b) investigators must report annual accrual and
progress in conducting analyses, as appropriate, by sex/gender and/or
racial/ethnic group differences.

Required Education
on the Protection of Human Subject Participants:NIH policy requires
education on the protection of human subject participants for all investigators
submitting NIH applications for research involving human subjects and
individuals designated as key personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

NIH Public Access Policy Requirement:In
accordance with the NIH Public Access Policy (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-08-033.html)
investigators must submit or have submitted for them their final, peer-reviewed
manuscripts that arise from NIH funds and are accepted for publication as of
April 7, 2008 to PubMed Central (http://www.pubmedcentral.nih.gov/), to be
made publicly available no later than 12 months after publication. As of May
27, 2008, investigators must include the PubMed Central reference number when
citing an article in NIH applications, proposals, and progress reports that
fall under the policy, and was authored or co-authored by the investigator or
arose from the investigator’s NIH award. For more information, see
the Public Access webpage at http://publicaccess.nih.gov/.

Standards
for Privacy of Individually Identifiable Health Information:The Department
of Health and Human Services (DHHS) issued final modification to the
"Standards for Privacy of Individually Identifiable Health
Information", the "Privacy Rule", on August 14, 2002. The
Privacy Rule is a federal regulation under the Health Insurance Portability and
Accountability Act (HIPAA) of 1996 that governs the protection of individually
identifiable health information, and is administered and enforced by the DHHS
Office for Civil Rights (OCR).

Decisions about applicability and implementation of
the Privacy Rule reside with the researcher and his/her institution. The OCR
website (http://www.hhs.gov/ocr/) provides information on the
Privacy Rule, including a complete Regulation Text and a set of decision tools
on "Am I a covered entity?" Information on the impact of the HIPAA
Privacy Rule on NIH processes involving the review, funding, and progress
monitoring of grants, cooperative agreements, and research contracts can be
found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs in NIH
Grant Applications or Appendices:
All
applications and proposals for NIH funding must be self-contained within
specified page limitations. For publications listed in the appendix and/or
Progress report, internet addresses (URLs) must be used for publicly accessible on-line journal articles. Unless otherwise specified in this solicitation, Internet addresses (URLs) should not be used to provide
any other information necessary for the review because reviewers are
under no obligation to view the Internet sites. Furthermore, we caution
reviewers that their anonymity may be compromised when they directly access an
Internet site.

Healthy
People 2010:The Public
Health Service (PHS) is committed to achieving the health promotion and disease
prevention objectives of "Healthy People 2010," a PHS-led national
activity for setting priority areas. This FOA is related to one or more of the
priority areas. Potential applicants may obtain a copy of "Healthy People
2010" at http://www.health.gov/healthypeople.

Authority and
Regulations:This
program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and is not subject to the
intergovernmental review requirements of Executive Order 12372. Awards are made
under the authorization of Sections 301 and 405 of the Public Health Service
Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR 52 and
45 CFR Parts 74 and 92. All awards are subject to the terms and conditions,
cost principles, and other considerations described in the NIH Grants Policy Statement. The NIH Grants Policy Statement
can be found at http://grants.nih.gov/grants/policy/policy.htm.

The PHS strongly
encourages all grant recipients to provide a smoke-free workplace and
discourage the use of all tobacco products. In addition, Public Law 103-227,
the Pro-Children Act of 1994, prohibits smoking in certain facilities (or in
some cases, any portion of a facility) in which regular or routine education,
library, day care, health care, or early childhood development services are
provided to children. This is consistent with the PHS mission to protect and
advance the physical and mental health of the American people.

Loan
Repayment Programs:NIH encourages
applications for educational loan repayment from qualified health professionals
who have made a commitment to pursue a research career involving clinical,
pediatric, contraception, infertility, and health disparities related areas.
The LRP is an important component of NIH's efforts to recruit and retain the
next generation of researchers by providing the means for developing a research
career unfettered by the burden of student loan debt. Note that an NIH grant is
not required for eligibility and concurrent career award and LRP applications
are encouraged. The periods of career award and LRP award may overlap providing
the LRP recipient with the required commitment of time and effort, as LRP
awardees must commit at least 50% of their time (at least 20 hours per week
based on a 40 hour week) for two years to the research. For further
information, please see: http://www.lrp.nih.gov.